Impact of F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in patients with biochemical evidence of recurrent or residual medullary thyroid cancer

Background: Conventional imaging such as with Tc-99m(V)dimercaptosunnic acid (DMSA), In-111-octreotide scintigraphy, computed tomography (CT), and magnetic resonance imaging (MRI) rarely localizes occult medullary thyroid cancer (MTC). The role of F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is not well defined. The aim of this study was to examine the usefulness of postoperative FDG-PET in localizing MTC metastases. Methods: FDG-PET was performed in 26 patients with elevated serum tumor markers after total thyroidectomy with central compartment dissection and additional neck dissection on indication. Patient- and lesion-based results were compared with the findings of conventional nuclear imaging and validated by morphological imaging (CT, MRI, ultrasonography), including bone scintigraphy and pathology when possible. Clinical impact was evaluated. Results: FDG-PET detected foci in 50% of patients with lesion-based sensitivity of 96%. In-111-octreotide detected foci in 19% with sensitivity of 41%, and Tc-99m(V)DMSA scintigraphy and morphological imaging detected foci in 21% and 40%, respectively, with sensitivity of 57% and 87%. No lesions were found in 11 patients (42%). Positive FDG-PET findings led to surgical intervention in nine patients (35%). They all underwent surgery for removal of residual tumor or metastases. One patient achieved disease-free status. In all patients who underwent surgery, serum calcitonin levels were reduced by an average of 58 +/- 31%. Conclusions: For detection of occult MTC lesions, FDG-PET is superior to conventional nuclear imaging and is the best detection method yet available. FDG-PET in postoperative follow-up has clinical value and may be used for guiding reoperation and additional morphological imaging preoperatively

Imatinib induces hypothyroidism in patients receiving levothyroxinc

Interactions of imatinib with other drugs have been scarcely reported. We report a previously unknown effect of imatinib on levothyroxine therapy. Eleven patients (1 with gastrointestinal stromal tumor and 10 with medullary thyroid carcinoma) received imatinib. Eight had undergone thyroidectomy and used levothyroxine, and 3 had the thyroid in situ. Thyroid function was measured before, during, and within 2 weeks after any change in either imatinib or levothyroxine dosage. We observed symptoms of hypothyroidism in all patients who had undergone thyroidectomy, whereas patients with the thyroid in situ remained clinically and biochemically euthyroid. On average, thyrotropin (INN, thyrotrophin) levels increased to 384% +/- 228% of the upper limit in patients after thyroidectomy, whereas free thyroxine (fT4) and free tri-iodothyronine (fT3) values remained within the reference range (59% +/- 17% of the upper limit for fT4 and 63% +/- 4% of the upper limit for fT3). Clinicians should be aware that hypothyroid subjects receiving imatinib have a high likelihood for increased levothyroxine replacement and should be closely monitored for elevations in thyrotropin indicating worsening hypothyroidism

Acceptable age for prophylactic surgery in children with multiple endocrine neoplasia type 2a

Aims: Germline mutated RET proto-oncogene, causing multiple endocrine neoplasia (MEN)-2a syndrome is the indication for prophylactic total thyroidectomy. Literature regarding the risk and the extent of early surgical intervention is scarce and the optimum age for surgery is still controversial. To optimize management in these young children we evaluate our experience and results. Patients and methods: From 1990 to 2001 preventive total thyroidectomy was performed in 13 MEN-2a gene carriers (4 boys and 9 girls; median age 7 (4-14) years). Preoperative assessment, surgical procedure, pathological examination, postoperative complications and treatment results were studied. Results: Surgery existed of a total thyroidectomy alone (n=3) in children with normal basal calcitonin and in combination with tracheo-esophageal exploration (n=6) or central compartment dissection (n=4) in case of abnormal calcitonin levels. Eight children presented with medullary thyroid cancer (MTC), three (median: 5 (4-12) years) with microscopic MTC and five (median 6 (4-14) years) with frank invasive MTC. Four of these five patients were younger than 6 years. Except for long-lasting hypoparathyroidism in one patient there were no complications. At a median follow-up of 6.5 years all patients are disease free. Conclusion: MTC in RET mutated MEN-2a gene carriers in childhood are found at the age of 4 years. Therefore, DNA testing should be done preferably before that age. Preventive surgery can be performed safely at that age and may be limited to total thyroidectomy when baseline calcitonin levels are normal. (C) 2002 Elsevier Science Ltd. All rights reserved

Clinical Relevance of F-18-FDG PET and F-18-DOPA PET in Recurrent Medullary Thyroid Carcinoma

The transition from stable to progressive disease is unpredictable in patients with biochemical evidence of medullary thyroid carcinoma (MTC). Calcitonin and carcinoembryonic antigen (CEA) doubling times are currently the most reliable markers for progression, but for accurate determination, serial measurements, which need time, are required. We compared F-18-FDG PET and F-18-dihydroxyphenylanaline (F-18-DOPA) PET with biochemical parameters and survival to assess whether these imaging modalities could be of value in detecting progressive disease. Methods: We evaluated the outcome of F-18-FDG PET or F-18-DOPA PET with calcitonin and CEA doubling times in 47 MTC patients. A subgroup of patients was included in the whole metabolic burden (WBMTB) analysis, with determination of standardized uptake values and number of lesions. WBMTB of F-18-DOPA PET and F-18-FDG PET was compared with biochemical parameters. Furthermore, survival was compared with F-18-DOPA PET or F-18-FDG PET positivity. Results: Doubling times were available for 38 of 40 patients undergoing F-18-FDG PET. There was a significant correlation with F-18-FDG PET positivity. Doubling times were less than 24 mo in 77% (n = 10/13) of F-18-FDG PET-positive patients, whereas 88% (n = 22/25) of F-18-FDG PET-negative patients had doubling times greater than 24 mo (P < 0.001). Between doubling times and F-18-DOPA PET positivity, no significant correlation existed. F-18-DOPA PET detected significantly more lesions (75%, 56/75) than did F-18-FDG PET (47%, 35/75) in the 21 patients included in WBMTB analysis (P = 0.009). Calcitonin and CEA levels correlated significantly with WBMTB on F-18-DOPA PET, but doubling times did not. F-18-FDG PET positivity was a more important indicator for poor survival in patients for whom both scans were obtained. Conclusion: F-18-FDG PET is superior in detecting patients with biochemical progressive disease and identifying patients with poor survival. Although F-18-DOPA PET has less prognostic value, it can more accurately assess the extent of the disease in patients with residual MTC. Hence, both scans are informative about tumor localization and behavior. On the basis of these results, we designed a clinical flow diagram for general practice in detecting recurrent MTC